Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu, China.
Department of Oncology, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, Jiangsu, China.
Cancer Med. 2024 Sep;13(17):e70247. doi: 10.1002/cam4.70247.
To explore the association between protein quantitative trait loci (pQTL-SNPs) and the risk of LUAD.
"Blood +" high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non-tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL-SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL-SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein.
A total of 7 pQTL-SNPs were significantly associated with altered LUAD risk (p < 0.05). Meanwhile, the expression of their corresponding target proteins were all decreased in both plasma and tumor tissues of LUAD cases, which may play a role of tumor suppressor proteins. After mutation of 3 pQTL-SNPs (rs7683000, rs73224660, and rs2776937), the expression of corresponding target proteins BST1 and NRP1 decreased, and as potential tumor suppressor proteins, which may promote tumorigenesis and further increasing the risk of developing LUAD (OR >1, p < 0.05); while after mutation the other pQTL-SNP rs62069916, the corresponding target protein APOH expression was increased, while as a potential tumor suppressor protein, which may inhibit tumorigenesis and further reduced the risk of developing LUAD (OR <1, p < 0.05). In addition, the expression of NRP1 and APOH were significant decreased in LUAD cell lines and validated in plasma of LUAD patients.
A total of 4 pQTL-SNPs (rs7683000, rs73224660, rs2776937, and rs62069916) may associate with altered LUAD risk by regulating the expression of target proteins (BST1, NRP1, and APOH) after mutation.
探索蛋白质数量性状基因座（pQTL-SNPs）与 LUAD 风险之间的关联。
对女性 LUAD 患者和女性健康对照者的血浆进行“血液+”高深度血液蛋白质组学分析，并结合女性 LUAD 患者肿瘤和相邻非肿瘤组织的蛋白质组学数据筛选在血浆和组织中均有表达的蛋白质。然后通过多个数据库筛选 pQTL-SNPs，并进行多层次筛选。通过亚洲女性肺癌联盟 GWAS（FLCCA GWAS）评估选定的 pQTL-SNPs 与 LUAD 风险之间的关联。酶联免疫吸附试验（ELISA）用于测定候选蛋白的水平。
共发现 7 个 pQTL-SNPs 与 LUAD 风险改变显著相关（p<0.05）。同时，LUAD 病例的血浆和肿瘤组织中其相应靶蛋白的表达均降低，可能发挥肿瘤抑制蛋白的作用。在 3 个 pQTL-SNPs（rs7683000、rs73224660 和 rs2776937）发生突变后，相应靶蛋白 BST1 和 NRP1 的表达降低，作为潜在的肿瘤抑制蛋白，可能促进肿瘤发生，进一步增加 LUAD 的发病风险（OR>1，p<0.05）；而另一个 pQTL-SNP rs62069916 发生突变后，相应靶蛋白 APOH 的表达增加，而作为潜在的肿瘤抑制蛋白，可能抑制肿瘤发生，进一步降低 LUAD 的发病风险（OR<1，p<0.05）。此外，NRP1 和 APOH 的表达在 LUAD 细胞系中显著降低，并在 LUAD 患者的血浆中得到验证。
共发现 4 个 pQTL-SNPs（rs7683000、rs73224660、rs2776937 和 rs62069916）可能通过调节突变后靶蛋白（BST1、NRP1 和 APOH）的表达与 LUAD 风险改变相关。
